间尼索地平控释微丸Beagle犬体内药动学研究

Pharmacokinetics of m-nisoldipine Controlled-release Pellets in Beagle Dogs

目的建立间尼索地平血药浓度的高效液相色谱-质谱联用方法,研究Beagle犬单剂量口服间尼索地平控释微丸的药动学。方法用HPLC-MS法测定健康Beagle犬单剂量口服间尼索地平控释微丸和普通微丸的血药浓度,以DAS 2.0软件计算药动学参数。结果单剂量给药后,控释微丸和普通微丸的tmax分别为(11.154±0.5077)h和(2.213±0.3225)h,Cmax分别为(79.40±10.60)ng.mL1和(116.7±20.35)ng.mL1,AUC分别为(1227.8±296.0)ng.h.mL1和(867.8±146.7)ng.h.mL1,控释微丸的相对生物利用度为141.5%。结论本方法准确、灵敏,间尼索地平控释微丸血药浓度平稳,可较长时间保持血药浓度。

OBJECTIVE To establish a method of HPLC-MS for studying the pharmacokinetics of m-nisoldipine controlled- release pellets after a single oral administrations in Beagle dogs. METHODS To determine the plasma concentrations of m-nisoldipine controlled-release pellets and conventional pellets after a single oral administration in Beagle dogs by HPLC-MS. The pharmacokinetic parameters were calculated by DAS 2.0 software. RESULTS The pharmacokinetic parameters for the single oral administration of controlled-release pellets and conventional pellets were tmax （11.154±0.5077）h and（2.213±0.3225）h, Cmax（79.40±10.60）ng.mL-1 and （116.7±20.35）ng.mL-1, AUC（1227.8±296.0）ng.h.mL-1 and （867.8±146.7）ng.h.mL-1, respectively. The relative bioavailability of controlled-release pellets was 141.5%. CONCLUSION The method of HPLC-MS is accurate and sensitive. The plasma concentration of m-nisoldipine controlled-release pellets is steady and the effective plasma drug concentration can be maintained for a longer time.